Journal article
Virus reactivation in acute and long COVID-19
Nature (London), Forthcoming
05 Aug 2026
PMID: 42557313
Featured in Collection : Drexel's Newest Publications
Abstract
Chronic viral infections are ubiquitous in humans, with individuals carrying multiple viruses that can reactivate during physiological stress, including severe illness
. Notably, SARS-CoV-2 infection has been shown to reactivate chronic viruses such as Epstein-Barr virus and cytomegalovirus, yet the full extent, temporal dynamics and immunological impact of viral reactivation in COVID-19 remain incompletely understood
. Here, leveraging multi-omic longitudinal data from 1,154 hospitalized patients with COVID-19 from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, we reveal significant reactivation of Herpesviridae and Anelloviridae during acute COVID-19, with distinct temporal dynamics for different viruses, and demonstrate that reactivation correlates with disease severity, host immune effects and clinical outcomes. Although our results do not establish causation between virus reactivation and clinical outcomes, we highlight the prevalence of chronic viral reactivation during acute COVID-19 and long COVID. Our findings challenge the prevailing view that chronic viral reactivation is primarily a consequence of immunosuppression, demonstrating that reactivations occur frequently in immunocompetent individuals during severe illness and in association with increased systemic inflammation. Additionally, we demonstrate persistence of viral reactivation in convalescence, and report an association of Anelloviridae with long COVID. This study provides immune, transcriptomic and metabolomic signatures of viral reactivation that could inform future strategies to prognosticate and treat acute COVID-19 and long COVID.
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Details
- Title
- Virus reactivation in acute and long COVID-19
- Creators
- Cole Maguire - The University of Texas at AustinJing Chen - Boston Children's HospitalNadine Rouphael - Emory UniversityBrinkley A Morse - Baylor College of MedicineAnnmarie Hoch - Boston Children's HospitalHarry Pickering - University of California, Los AngelesHoang Van Phan - University of California, San FranciscoAbigail Glascock - Chan Zuckerberg Initiative (United States)Victoria Chu - University of California, San FranciscoRavi Dandekar - University of California, San FranciscoDavid Corry - Baylor College of MedicineFarrah Kheradmand - Baylor College of MedicineLindsey R Baden - Brigham and Women's HospitalRafick-Pierre Sekaly - Case Western Reserve UniversityGrace A McComsey - University Hospitals of ClevelandElias K Haddad - Drexel UniversityCharles B Cairns - Drexel UniversityBali Pulendran - Palo Alto UniversityAna Fernandez-Sesma - Icahn School of Medicine at Mount SinaiViviana Simon - Icahn School of Medicine at Mount SinaiJordan P Metcalf - University of Oklahoma Health Sciences CenterNelson I Agudelo Higuita - OU HealthWilliam B Messer - Oregon Health & Science UniversityMark M Davis - Stanford UniversityKari C Nadeau - Stanford UniversityMonica Kraft - University of ArizonaChris Bime - University of ArizonaJoanna Schaenman - University of California, Los AngelesDavid Erle - University of California, San FranciscoCarolyn S Calfee - University of California, San FranciscoMark A Atkinson - University of FloridaScott C Brakenridge - University of FloridaLauren I R Ehrlich - The University of Texas at AustinRuth R Montgomery - Yale UniversityAlbert Shaw - Yale UniversityCatherine L Hough - Oregon Health & Science UniversityDavid Hafler - Yale UniversityAlison D Augustine - National Institute of Allergy and Infectious DiseasesPatrice M Becker - National Institute of Allergy and Infectious DiseasesBjoern Peters - La Jolla Institute for ImmunologyAl Ozonoff - Boston Children's HospitalSeunghee Kim-Schulze - Icahn School of Medicine at Mount SinaiFlorian Krammer - Icahn School of Medicine at Mount SinaiSteven E Bosinger - Emory UniversityWalter Eckalbar - University of California, San FranciscoMatthew C Altman - University of WashingtonMichael Wilson - University of California, San FranciscoLeying Guan - Yale UniversitySteven H Kleinstein - Yale UniversityKinga K Smolen - Boston Children's HospitalElaine F Reed - University of California, Los AngelesOfer Levy - Broad InstituteHolden Maecker - Stanford UniversityPeter Hunt - University of California, San FranciscoHanno Steen - Boston Children's HospitalJoann Diray-Arce - Boston Children's HospitalCharles R Langelier - University of California, San FranciscoEsther Melamed (Corresponding Author) - The University of Texas at Austin
- Publication Details
- Nature (London), Forthcoming
- Publisher
- Nature Publishing
- Number of pages
- 36
- Grant note
- National Institutes of Health's National Institute on Drug Abuse: 5T32DA018926-18 National Institutes of Health's National Institute of Allergy and Infectious Diseases: 5R01AI104870-07, 5R01AI135803-03, 3U19AI077439-13, AI089992, 4U19AI090023-11, 5U19AI118608-04, 4U19AI118610-06, 5U19AI057229-18, 5U19AI125357-05, 3U19AI128913-03, 5U19AI128913-03, 5U19AI128910-04, 5U54AI142766-03, R01AI145835-01A1S1 National Institute of Diabetes, Digestive, and Kidney Disease: R01DK130425 National Institutes of Health's National Institute on Alcohol Abuse and Alcoholism: K08 AA027837-05 National Institutes of Health's National Center for Advancing Translational Sciences: UM1TR004528 Division of Intramural Research of the National Institute of Allergy and Infectious Diseases
C.M. discloses funding from National Institutes of Health's National Institute on Drug Abuse (5T32DA018926-18). E.M. and L.I.R.E. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (5R01AI104870-07). J.C., A.H., L.R.B., A.O., K.K.S., O.L., H.S. and J.D.-A. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (5U19AI118608-04). N.R., R.-P.S. and S.E.B. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (4U19AI090023-11). H.C.P., J.S. and E.F.R. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (5U19AI128913-03). H.V.P., R.D., D.J.E., C.S.C., W.E., M.W., P.H. and C.R.L. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (3U19AI077439-13). D.B.C. and F. Kheradmand disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (5R01AI135803-03). E.K.H. and C.B.C. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (5U19AI128910-04). B. Pulendran, J.P.M., N.I.A.H., W.B.M., M.M.D., K.C.N. and H.M. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (5U19AI057229-18). A.F.S., V.S., S.K.-S. and F. Krammer disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (4U19AI118610-06). C.B. and M.K. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (5U19AI125357-05). M.A.A. and S.C.B. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (5U54AI142766-03, P01AI042288) and National Institute of Diabetes, Digestive, and Kidney Disease (R01DK130425). R.R.M., A.S., D.A.H., L.G. and S.H.K. disclose funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (AI089992). C.L.H. discloses funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (R01AI145835-01A1S1). E.M. discloses funding from National Institutes of Health's National Institute on Alcohol Abuse and Alcoholism (K08 AA027837-05). G.A.M. discloses funding from National Institutes of Health's National Center for Advancing Translational Sciences (UM1TR004528). A.D.A. and P.M.B. disclose funding from the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases. M.C.A. discloses funding from the National Institutes of Health's National Institute of Allergy and Infectious Diseases (5U19AI167891-05 and 5R01AI132774-03). V.C. discloses funding from the National Institutes of Health's National Institute of Allergy and Infectious Diseases (1K23AI185326). The IMPACC Network discloses funding from National Institutes of Health's National Institute of Allergy and Infectious Diseases (5R01AI104870-07, 5R01AI135803-03, 3U19AI077439-13, AI089992, 4U19AI090023-11, 5U19AI118608-04, 4U19AI118610-06, 5U19AI057229-18, 5U19AI125357-05, 3U19AI128913-03, 5U19AI128913-03, 5U19AI128910-04, 5U54AI142766-03 and R01AI145835-01A1S1). B.A.M., A.G. and B. Peters. declare no relevant funding.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Emergency Medicine
- Web of Science ID
- WOS:001840766600001
- Other Identifier
- 991022201459504721